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  1. Article: The neutrophil to lymphocyte ratio associates with markers of Alzheimer's disease pathology in cognitively unimpaired elderly people.

    Jacobs, Tovia / Jacobson, Sean R / Fortea, Juan / Berger, Jeffrey S / Vedvyas, Alok / Marsh, Karyn / He, Tianshe / Gutierrez-Jimenez, Eugenio / Fillmore, Nathanael R / Bubu, Omonigho M / Gonzalez, Moses / Figueredo, Luisa / Gaggi, Naomi L / Plaska, Chelsea Reichert / Pomara, Nunzio / Blessing, Esther / Betensky, Rebecca / Rusinek, Henry / Zetterberg, Henrik /
    Blennow, Kaj / Glodzik, Lidia / Wisniewski, Thomas M / Leon, Mony J / Osorio, Ricardo S / Ramos-Cejudo, Jaime

    Research square

    2024  

    Abstract: Background: An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into ... ...

    Abstract Background: An elevated neutrophil-lymphocyte ratio (NLR) in blood has been associated with Alzheimer's disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-β42 (Aβ42), total tau (t-tau), and phosphorylated tau
    Results: A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β=-12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p = 0.019) and p-tau (β = 3.441, p = 0.015), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ+ (n = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p = 0.037) compared to Aβ- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data.
    Conclusions: We report associations between the NLR and Aβ42 in the older ADNI cohort, and between the NLR and t-tau and p-tau
    Language English
    Publishing date 2024-03-14
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-4076789/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pre-treatment differential correlation of gene expression and response to topical steroids in eosinophilic esophagitis.

    Dellon, Evan S / Tsai, Yihsuan S / Coffey, Alisha R / Bodwin, Kelly / Sninsky, Jared A / Mosso, Carson N / He, Tianshe M / O'Connor, Kevin A / Selitsky, Sara R / Nobel, Andrew B / Parker, Joel S

    Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus

    2022  Volume 36, Issue 4

    Abstract: Few predictors of response to topical corticosteroid (tCS) treatment have been identified in eosinophilic esophagitis (EoE). We aimed to determine whether baseline gene expression predicts histologic response to tCS treatment for EoE. We analyzed ... ...

    Abstract Few predictors of response to topical corticosteroid (tCS) treatment have been identified in eosinophilic esophagitis (EoE). We aimed to determine whether baseline gene expression predicts histologic response to tCS treatment for EoE. We analyzed prospectively collected samples from incident EoE cases who were treated with tCS for 8 weeks in a development cohort (prospective study) or in an independent validation cohort (clinical trial). Whole transcriptome RNA expression was determined from a baseline (pre-treatment) RNA-later preserved esophageal biopsy. Baseline expression was compared between histologic responders (<15 eos/hpf) and non-responders (≥15 eos/hpf), and differential correlation was used to assess baseline gene expression by response status. In 87 EoE cases analyzed in the development set, there were no differentially expressed genes associated with treatment response (at false discovery rate = 0.1). However, differential correlation identified a module of 22 genes with statistically significantly high pairwise correlation in non-responders (mean correlation coefficient = 0.7) compared to low correlation in responders (coefficient = 0.3). When this 22-gene module was applied to the 89 EoE cases in the independent cohort, it was not validated to predict tCS response at the 15 eos/hpf threshold (mean correlation coefficient = 0.32 in responders and 0.25 in nonresponders). Exploration of other thresholds also did not validate any modules. Though we identified a 22 gene differential correlation module measured pre-treatment that was strongly associated with subsequent histologic response to tCS in EoE, this was not validated in an independent population. Alternative methods to predict steroid response should be explored.
    MeSH term(s) Humans ; Eosinophilic Esophagitis/drug therapy ; Eosinophilic Esophagitis/genetics ; Eosinophilic Esophagitis/complications ; Prospective Studies ; Glucocorticoids/therapeutic use ; Steroids/therapeutic use ; Gene Expression
    Chemical Substances Glucocorticoids ; Steroids
    Language English
    Publishing date 2022-10-11
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639470-x
    ISSN 1442-2050 ; 1120-8694
    ISSN (online) 1442-2050
    ISSN 1120-8694
    DOI 10.1093/dote/doac071
    Database MEDical Literature Analysis and Retrieval System OnLINE

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